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1.
Front Cell Dev Biol ; 11: 1252953, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38033869

RESUMEN

Ionotropic glutamate receptors (iGluRs) mediate the majority of excitatory neurotransmission and are implicated in various neurological disorders. In this review, we discuss the role of the two fastest iGluRs subtypes, namely, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors, in the pathogenesis and treatment of Parkinson's disease, epilepsy, and amyotrophic lateral sclerosis. Although both AMPA and kainate receptors represent promising therapeutic targets for the treatment of these diseases, many of their antagonists show adverse side effects. Further studies of factors affecting the selective subunit expression and trafficking of AMPA and kainate receptors, and a reasonable approach to their regulation by the recently identified novel compounds remain promising directions for pharmacological research.

2.
Genes (Basel) ; 14(7)2023 06 24.
Artículo en Inglés | MEDLINE | ID: mdl-37510237

RESUMEN

A 60-year-old male with hypertrophic cardiomyopathy, conduction disorders, post-COVID-19 myopericarditis and heart failure was admitted to the hospital's cardiology department. Blood tests revealed an increase in CPK activity, troponin T elevation and high titers of anticardiac antibodies. Whole exome sequencing showed the presence of the pathogenic variant NM_213599:c.2272C>T of the ANO5 gene. Results of the skeletal muscle biopsy excluded the diagnosis of systemic amyloidosis. Microscopy of the muscle fragment demonstrated sclerosis of the perimysium, moderate lymphoid infiltration, sclerosis of the microvessels, dystrophic changes and a lack of cross striations in the muscle fibers. Hypertrophy of the LV with a low contractile ability, atrial fibrillation, weakness of the distal skeletal muscles and increased plasma CPK activity and the results of the skeletal muscle biopsy suggested a diagnosis of a late form of distal myopathy (Miyoshi-like distal myopathy, MMD3). Post-COVID-19 myopericarditis, for which genetically modified myocardium could serve as a favorable background, caused heart failure decompensation.


Asunto(s)
COVID-19 , Cardiomiopatía Hipertrófica , Miopatías Distales , Insuficiencia Cardíaca , Miocarditis , Masculino , Humanos , Persona de Mediana Edad , Miopatías Distales/diagnóstico , Miopatías Distales/genética , Miopatías Distales/patología , Esclerosis/patología , Anoctaminas/genética , Canales de Cloruro/genética , Mutación , COVID-19/complicaciones , COVID-19/genética , COVID-19/patología , Músculo Esquelético/patología , Cardiomiopatía Hipertrófica/complicaciones , Cardiomiopatía Hipertrófica/genética , Cardiomiopatía Hipertrófica/patología , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/patología
3.
Free Radic Biol Med ; 159: 15-22, 2020 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-32738397

RESUMEN

Adrenaline or epinephrine is a hormone playing an important role in physiology. It is produced de-novo in the brain in very small amounts compared to other catecholamines, including noradrenaline. Although the effects of adrenaline on neurons have been extensively studied, much less is known about the action of this hormone on astrocytes. Here, we studied the effects of adrenaline on astrocytes in primary co-culture of neurons and astrocytes. Application of adrenaline induced calcium signal in both neurons and astrocytes, but only in neurons this effect was dependent on α- and ß-receptor antagonists. The effects of adrenaline on astrocytes were less dependent on adrenoreceptors: the antagonist carvedilol had only moderate effect on the calcium signal and the agonist of adrenoreceptors methoxamine induced a signal only in small proportion of the cells. We found that adrenaline in astrocytes activates phospholipase C and subsequent release of calcium from the endoplasmic reticulum. Calcium signal in astrocytes is initiated by the metabolism of adrenaline by the monoamine oxidase (MAO), which activates reactive oxygen species production and induces lipid peroxidation. Inhibitor of MAO selegiline inhibited both adrenaline-induced calcium signal in astrocytes and the vasoconstriction that indicates an important role for monoamine oxidase in adrenaline-induced signalling and function.


Asunto(s)
Astrocitos , Monoaminooxidasa , Calcio , Epinefrina/farmacología , Inhibidores de la Monoaminooxidasa , Vasoconstricción
4.
Curr Med Chem ; 26(3): 487-505, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-28990520

RESUMEN

Nowadays, enzymatic therapy is a very promising line of treatment for many different diseases. There is a group of disorders and conditions, caused by fibrotic and scar processes and associated with the excessive accumulation of collagen that needs to be catabolized to normalize the connective tissue content. The human body normally synthesizes special extracellular enzymes, matrix metalloproteases (MMPs) by itself. These enzymes can cleave components of extracellular matrix (ECM) and different types of collagen and thus maintain the balance of the connective tissue components. MMPs are multifunctional enzymes and are involved in a variety of organism processes. However, under pathological conditions, the function of MMPs is not sufficient, and these enzymes fail to deal with disease. Thus, medical intervention is required. Enzymatic therapy is a very effective way of treating such collagen-associated conditions. It involves the application of exogenous collagenolytic enzymes that catabolize excessive collagen at the affected site and lead to the successful elimination of disease. Such collagenolytic enzymes are synthesized by many organisms: bacteria, animals (especially marine organisms), plants and fungi. The most studied and commercially available are collagenases from Clostridium histolyticum and from the pancreas of the crab Paralithodes camtschatica, due to their ability to effectively hydrolyse human collagen without affecting other tissues, and their wide pH ranges of collagenolytic activity. In the present review, we summarize not only the data concerning existing collagenase-based medications and their applications in different collagen-related diseases and conditions, but we also propose collagenases from different sources for their potential application in enzymatic therapy.


Asunto(s)
Colágeno/metabolismo , Colagenasas/metabolismo , Animales , Colagenasas/uso terapéutico , Matriz Extracelular/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Humanos , Concentración de Iones de Hidrógeno , Metaloproteinasas de la Matriz/metabolismo , Proteolisis , Terapéutica
5.
Curr Med Chem ; 26(3): 506-516, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-29210638

RESUMEN

Collagen and collagen-based materials have been successfully used in medicine for over 50 years. The number of scientific articles about the role of collagen in the construction of scaffolds for tissue engineering has risen precipitously in recent years. The review contains materials about historic and modern applications of collagen in medicine such as soluble collagen injections, solid constructs reconstructed from solution, and decellularized collagen matrices. The analysis of published data proves the efficacy of collagen material in the treatment of chronic wounds, burns, venous and diabetic ulcers, in plastic, reconstructive and general surgery, urology, proctology, gynecology, ophthalmology, otolaryngology, neurosurgery, dentistry, cardiovascular and bone and cartilage surgery, as well as in cosmetology. Further development of collagenoplasty requires addressing the problems of allergic complications, improvement of structure and maximizing therapeutic effects against pathological processes.


Asunto(s)
Materiales Biocompatibles , Colágeno/uso terapéutico , Colágeno/química , Humanos , Medicina
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